Pancreatic Cancer: The Basics

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What is the Pancreas?

The pancreas is a pear-shaped gland, about six inches in length, located deep within the abdomen, between the stomach and the spine. It is referred to in three parts: the widest part is called the head, the middle section is the body, and the thin end is called the tail. The pancreas is responsible for making hormones, including insulin, which help to regulate blood sugar levels, and enzymes, which are used by the bowel for the digestion of food. These enzymes are transported through ducts within the pancreas, emptied into the common bile duct, which carries the enzymes into the bowel.

What is Pancreatic Cancer?

Pancreatic cancer happens when cells in the pancreas begin to grow uncontrolled, without any "checks and balances." These "out of control" cancer cells then have the ability to spread to nearby lymph nodes and organs (such as the liver and lungs). When cancer spreads, it is called metastatic. About seventy percent of pancreatic cancers occur in the head of the pancreas, and most of these begin in the ducts that carry the enzymes. The vast majority of pancreatic cancers are of ductal origin and are referred to as pancreatic adenocarcinoma. There are other types of pancreatic cancer with different (non-ductal) cell origins, which make up a small minority of pancreatic cancers.

Am I at Risk For Pancreatic Cancer?

The incidence of pancreatic cancer is highest between 60 and 80 years of age, and is only rarely seen in people under 40. It is seen about equally in men and women, although the rates in women have risen in recent years, which may be due to higher rates of smoking in women. Cigarette smokers are two to three times more likely to develop pancreatic cancer. It is slightly more common in blacks and members of the Jewish community. It is seen more commonly in people who have diabetes and obese people, but this link is not yet well understood.

Certain occupational exposures are thought to put a person at higher risk. These include chemists, coal, gas, and metal workers, and those employed in industries where pesticides are used more frequently. A person's risk triples if his/her mother, father, or siblings have had the disease. A family history of breast or colon cancer also increases risk. This increased risk is due to inherited mutations in cancer-causing genes (changes that allow cancer to develop). The actual cause of this disease is not known, but is thought to be a result of a combination of inherited genetic changes and changes caused by environmental exposures.

How Can I Prevent Pancreatic Cancer?

Unfortunately, no one really knows what causes the disease, so it is difficult to prevent. One important point is that the risk for smokers who quit does decrease; so giving up cigarettes is helpful. Be aware of your family's health history. This can make you and your healthcare providers aware of any increased risk.

What Screening Tests are Available?

There are no screening tests currently available for pancreatic cancer. Researchers have been able to discover the genetic changes present in cancer of the pancreas. These genes are detectable in stool, bowel and enzyme fluid, bile, and blood. Researchers are looking at these genes as a potential way to screen people for pancreatic cancer in the future.

For patients with familial genetic syndromes that are linked to pancreatic cancer (hereditary pancreatitis, Peutz-Jeghers syndrome (PJS), BRCA2 mutations and familial atypical multiple mole melanoma (FAMMM) syndrome), screening should be considered. This screening would begin 10 years earlier than the time by when the disease is typically seen. For example, people with PJS tend to develop pancreatic cancer at an average age of 40, so screening would begin at age 30. Patients known to have these genetic syndromes should be followed by specialists in that syndrome. Studies that are used for screening include: CT scan, MRI, and EUS (endoscopic ultrasound), but these current methods are costly and researchers are looking for more cost- effective techniques.

What are the Signs of Pancreatic Cancer?

Unfortunately, the signs of early stage pancreatic cancer are vague, and often attributed to other problems by both patients and physicians. More specific symptoms tend to develop after the tumor has advanced and grown to invade other organs or blocked the bile ducts. Symptoms include weight loss, loss of appetite, jaundice (a condition that causes yellowing of the eyes and skin and darkening of urine), pain in the upper abdomen or back, weakness, or nausea and vomiting. These symptoms can vary depending on where the tumor is located in the pancreas (head, body or tail). Newly developed diabetes is the presenting sign in ten to twenty percent of patients. This is caused by the cancerous pancreas' inability to produce insulin.

How is Pancreatic Cancer Diagnosed and Staged?

When a physician suspects that a patient may have pancreatic cancer there are several tests that can be done to make a diagnosis. A high quality CT Scan (called a spiral or helical CT) can detect a tumor in the pancreas, enlarged lymph nodes (which may indicate tumor involvement), tumors in the liver, or obstructions of the bile duct. It is the test most commonly used to diagnose this cancer in the United States. Ultrasound can also be used and is the more commonly used test in other areas of the world. Ultrasound uses a device that emits sound waves, which bounce off the organs, producing echoes that are used to create an image of the organ. This can be done on the outside of the abdomen (called transabdominal ultrasound) or from inside the bowel (a catheter is passed through the mouth down to the bowel), this is called endoscopic ultrasound or EUS.

If a patient has jaundice, the doctor may want to do a test to find out where the bile duct is blocked and if this blockage is caused by a tumor or another condition. Tests that can determine this are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). In ERCP, a tube is passed through the mouth down the throat to the bowel, where a small catheter is inserted into the bile and pancreatic ducts. Dye is injected and x-rays are taken. The x-rays will show where the blockage is and what it is caused by. In PTC, dye is injected through a needle that is inserted through the skin, into the liver. The dye moves into the bile ducts, again allowing the blockage and its cause to be seen with an x-ray. In some cases, a small sample of tissue (biopsy) may be removed during these procedures to be examined by a pathologist.

Some patients with pancreatic cancer may have an elevated level of carbohydrate antigen 19-9 (CA 19-9), but this is not present in all cases and may be caused by other things. In patients who have an elevated level, it is useful in confirming a diagnosis in conjunction with radiology tests and for monitoring the disease during treatment. The level can be periodically checked during treatment to see if the cancer is stable or worsening.

When the physicians talk about staging, they are referring to determining the size of the tumor and if it has spread or not. This information is then used to determine the best treatment. In the case of pancreatic cancer, the size of the tumor and whether or not it involves important blood vessels determines if it can be surgically removed. Pancreatic cancer is staged on the TNM system (also called tumor - node - metastasis system). This describes the size of the tumor (T), if the lymph nodes are involved (N), and if it has spread to other areas of the body (M). Practically speaking, pancreatic tumors are generally categorized as either resectable or unresectable, meaning whether or not they can be surgically removed. This depends on not only the size and spread, but whether or not critical structures (for example, major blood vessels) are involved.

Primary Tumor:

Tis: "In situ"

T1: Tumor confined to the pancreas, 2 cm or less

T2: Tumor confined to the pancreas, greater than 2 cm

T3: Tumor extending beyond the pancreas, but not involving the superior mesenteric artery or celiac axis

T4: Tumor involves the superior mesenteric artery or celiac axis

Lymph Nodes:

N0: No lymph node involvement

N1: Lymph nodes are positive for cancer

Metastasis:

M0: No distant metastases

M1: Distant metastases are present.

Stage

T

N

M

0

Tis

N0

M0

I

T1-T2

N0

M0

II

T3

N0

M0

III

T1-3

N1

M0

IVA

T4

Any N

M0

IVB

Any T

Any N

M1

What are the Treatments For Pancreatic Cancer?

Approximately 10% of patients have localized tumors that are able to be surgically removed (generally stages I & II), offering the best hope for a cure. This surgery, called a Whipple procedure or pancreaticoduodenectomy, is an extensive and complicated one, and recovery can be difficult for the patient. For this reason, it is important to only perform the procedure on patients with small, resectable tumors who are likely to benefit. Recent studies have found that mortality (death) due to surgical complications is greatly decreased (to 1-4%) when the procedure is performed at regional referral centers that perform greater than 40 Whipple procedures per year. Even with curative resection, the tumor will recur without further treatment. These patients are treated with chemotherapy and radiation therapy after surgery (called adjuvant therapy) to provide the best chance of cure.

About 40% of patients will present with tumors that cannot be surgically removed, but have not yet spread to distant organs (called locally advanced). For these patients, chemotherapy and radiation is standard. Radiation is used to decrease the risk of the tumor recurring in the original area, while the chemotherapy is used to treat any stray cancer cells in the rest of the body, decreasing the risk of distant metastases. Chemotherapy agents are chosen for their ability to both kill cancer cells and make cells more sensitive to radiation (called radiosensitization). In some cases, the chemotherapy and radiation provides enough tumor shrinkage such that the patient may be able to have surgery later.

While these therapies for pancreatic cancer have not resulted in many cures, new therapies and combinations of existing therapies are allowing patients to live longer and have a better quality of life. Sadly, the average survival for these patients is still only six to twelve months.

Patients with disease that has spread to other organs are usually treated with either chemotherapy alone or palliative care, which aims to improve quality of life by controlling pain and other symptoms. Palliative care can consist of pain medications, radiation therapy, or nerve blocks to control pain, and biliary stents to relieve symptoms of a bile duct obstruction. Unfortunately, even with treatment these patients have an average survival of three to six months.

Due to the poor results with standard therapies, patients may choose to participate in clinical trials which test newly developed medications. Patients can discuss available clinical trials with their physician.

Follow-up Testing

After completion of therapy, patients are followed closely with CT scans and tumor marker levels (CA 19-9) for any sign of recurrence.